Synthesis, Molecular Docking and Molecular Dynamics Simulation Studies of Some Pyridazinone Derivatives as Lipase Inhibitors


Alagöz M., Doğan İ. S., Şener S. Ö., Özdemir Z.

CUMHURIYET SCIENCE JOURNAL, cilt.43, sa.3, ss.391-397, 2022 (Hakemli Dergi) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 3
  • Basım Tarihi: 2022
  • Doi Numarası: 10.17776/csj.1135400
  • Dergi Adı: CUMHURIYET SCIENCE JOURNAL
  • Derginin Tarandığı İndeksler: TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.391-397
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Human health and illness are dependent on lipases, which play a key role in maintaining cell integrity, storing fat for energy and serving as signaling molecules. In this study, 4 compounds that carry 6-phenylpyridazin-3(2H)-one main nucleus, which can be effective as lipase inhibitors, were synthesized and their structures were elucidated. The biological activity of synthesized compounds was evaluated via the porcine pancreatic lipase type II (PLL) inhibitor assay. Orlistat, a lipase inhibitor, was used as a positive control. Compound 8d was found to be the most effective compound, with an IC50 value of 32.66±2.8265 (μg/mL). In addition, molecular docking and molecular dynamics simulations studies were carried out to examine the interactions of the compounds with the target in detail. The results obtained as a result of these in silico studies were found to be compatible with the lipase inhibition effects of the compounds. It was observed that the compounds may have potential lipase inhibitory effects as a result of the substitutions of the 3-(6-oxo-3-phenylpyridazin-1(6H)-yl)propanehydrazide structure.